# YeastPathways -> module crosswalk. # # Every YeastPathways (SGD YeastCyc) pathway and every metabolic PomBase GO-CAM # is assigned to a module group. Groups are deliberately coarser than YeastCyc: # YeastCyc splits superpathways, variants and single reactions into separate # frames, whereas a module is a reusable biological unit at the level at which # the biology generalises across taxa. When a single frame spans two existing # modules, the frame is deliberately listed under both module groups. # # action: # NEW - no adequate module exists; create one at the stated scope. # ALIGN - an existing taxon-neutral module covers the chemistry; add fungal # variants/representatives, GO-CAM associations and evidence. # GENERALIZE - an existing module is written for one lineage (usually human); # broaden title/description and add a fungal variant without losing # the lineage-specific content. # FOLD - pathway is a single reaction or fragment; it is recorded inside # the named module rather than as a module of its own. # NOTE - no module: pathway hole (no yeast enzyme), grab-bag frame, or a # single-enzyme frame with no reusable boundary; see `rationale`. # # scope: the generalisation level chosen for the module. # # Pathway ids are YeastCyc frame ids (https://pathway.yeastgenome.org/YEAST/ # NEW-IMAGE?object=); `gocam` lists production GO-CAM ids (YeastPathways_* # models are the YeastPathways2GO conversions, GO_REF:0000123; bare hex ids are # PomBase models). groups: # ---------------------------------------------------------------- amino acids - module: histidine_biosynthesis action: ALIGN scope: cellular organisms with the His pathway (bacteria, archaea, fungi, plants) pathways: [HISTSYN-PWY] gocam: [YeastPathways_HISTSYN-PWY, 6690711d00002904] rationale: >- Existing module is already family-level with architecture variants. Fungi add two fusion architectures that must be explicit variants: the trifunctional HIS4 (HisI-HisE-HisD) and the bifunctional HIS7 (HisH-HisF glutamine amidotransferase/cyclase). Fungal HIS2 is a PHP-family histidinol-phosphatase, a third independent phosphatase origin. - module: arginine_biosynthesis action: ALIGN scope: acetyl-cycle (recycling) arginine biosynthesis in microbes and fungi pathways: [ARGSYNBSUB-PWY, CITRUL-BIO2-PWY] gocam: [YeastPathways_ARGSYNBSUB-PWY, YeastPathways_CITRUL-BIO2-PWY, 6690711d00000916] rationale: >- Fungi run the cyclic (ornithine acetyltransferase, ARG7) route split between mitochondrion (glutamate -> ornithine) and cytosol (ornithine -> arginine), with a fused ARG5,6 kinase/reductase polyprotein and an arginine-specific carbamoyl-phosphate synthetase (CPA1/CPA2) distinct from the pyrimidine CPSase-ATCase (URA2). Citrulline biosynthesis is a fragment of this pathway and is folded in. - module: lysine_biosynthesis_aminoadipate action: NEW scope: alpha-aminoadipate (AAA) pathway in fungi and the LysW-carrier AAA pathway of Thermus/Sulfolobus pathways: [LYSINE-AMINOAD-PWY-2] gocam: [YeastPathways_LYSINE-AMINOAD-PWY-2, 667dfe8d00001131] rationale: >- Existing lysine_biosynthesis is the bacterial diaminopimelate pathway, chemically unrelated. The AAA pathway is the right generalisation: the homocitrate -> 2-oxoadipate half is shared by fungi and LysW-type prokaryotes (homologous to the leucine/TCA aconitase and isocitrate dehydrogenase steps), while the 2-aminoadipate -> lysine half diverges (fungal LYS2 adenylation/reduction + saccharopine route vs. LysW-protected ArgBCDE-like route). Model the second half as a variant set. - module: branched_chain_amino_acid_biosynthesis action: ALIGN scope: cellular organisms (bacteria, fungi, plants) pathways: [BRANCHED-CHAIN-AA-SYN-PWY-1, ILEUSYN-PWY-1, VALSYN-PWY, LEUSYN-PWY-1] gocam: [YeastPathways_BRANCHED-CHAIN-AA-SYN-PWY-1, YeastPathways_ILEUSYN-PWY-1, YeastPathways_VALSYN-PWY, YeastPathways_LEUSYN-PWY-1, 6690711d00002706] rationale: >- Existing module already models the shared ILV2/ILV6-ILV5-ILV3 trunk and leucine branch. Fungal specifics: the mitochondrial location of the shared trunk and of alpha-IPM synthesis, alpha-IPM export, cytosolic LEU1/LEU2, and the BAT1 (mitochondrial)/BAT2 (cytosolic) transaminase paralog pair from the whole-genome duplication. - module: bacterial_shikimate_chorismate_biosynthesis action: GENERALIZE scope: shikimate pathway in bacteria, fungi, plants and apicomplexa pathways: [ARO-PWY-1] gocam: [YeastPathways_ARO-PWY-1, 67369e7600004623] rationale: >- The seven reactions are universal; fungi encode steps 2-6 in the pentafunctional AROM polypeptide (ARO1), which is the main architectural variant. Keep the slug; broaden the title/description and add an AROM fusion variant rather than creating a parallel fungal module. - module: phenylalanine_tyrosine_biosynthesis action: NEW scope: chorismate -> phenylalanine/tyrosine in bacteria, fungi and plants (prephenate and arogenate routes) pathways: [COMPLETE-ARO-PWY-1, PWY3O-4153, PWY3O-4120] gocam: [YeastPathways_COMPLETE-ARO-PWY-1, YeastPathways_PWY3O-4153, YeastPathways_PWY3O-4120, 67369e7600004623] rationale: >- No module covers the chorismate-mutase branch. The generalisation is a branch module with a route variant set: fungi/most bacteria use the prephenate route (PHA2 prephenate dehydratase, TYR1 prephenate dehydrogenase, then ARO8/ARO9 transamination), plants and some bacteria transaminate first (arogenate route). The superpathway frame is the union of the shikimate, tryptophan and this module and is not modelled itself. - module: tryptophan_biosynthesis action: ALIGN scope: microbial and plant tryptophan biosynthesis pathways: [TRPSYN-PWY-1] gocam: [YeastPathways_TRPSYN-PWY-1, 67369e7600004623] rationale: >- Existing microbial module. Fungal fusion variants: TRP3 (TrpG glutamine-amidotransferase + TrpC indole-3-glycerol-phosphate synthase) and TRP5 (fused TrpA-TrpB tryptophan synthase), TRP2/TRP3 anthranilate synthase. - module: phosphorylated_serine_biosynthesis action: ALIGN scope: cellular organisms pathways: [SERSYN-PWY] gocam: [YeastPathways_SERSYN-PWY, 6690711d00001545] rationale: >- Taxon-neutral three-step module already; add SER3/SER33, SER1, SER2 and fission yeast exemplars. Yeast also makes serine from glycine (SHMT reverse) and glyoxylate (AGX1/SHM); those routes are in glycine_serine_interconversion. - module: glycine_serine_interconversion action: NEW scope: eukaryotic and microbial glycine supply routes pathways: [PWY3O-261, GLYSYN-PWY, GLYSYN-THR-PWY, GLYSYN-ALA-PWY, PWY3O-230] gocam: [YeastPathways_PWY3O-261] rationale: >- YeastCyc has five frames for glycine/serine formation, each one reaction. Biologically they are alternative routes into one glycine pool: serine hydroxymethyltransferase (cytosolic SHM2 / mitochondrial SHM1), threonine aldolase (GLY1, the main route in S. cerevisiae), and alanine:glyoxylate aminotransferase (AGX1). Model as a variant set of glycine-forming routes; the glycine cleavage system is separate. - module: aspartate_family_threonine_biosynthesis action: NEW scope: aspartate -> homoserine -> threonine in bacteria, fungi and plants pathways: [THRESYN-PWY, PWY3O-7, P4-PWY-1, HOMOSERSYN-PWY, HOMOSER-THRESYN-PWY] gocam: [YeastPathways_THRESYN-PWY, YeastPathways_PWY3O-7, YeastPathways_P4-PWY-1, YeastPathways_HOMOSERSYN-PWY, YeastPathways_HOMOSER-THRESYN-PWY, 678073a900003175] rationale: >- The aspartate-family trunk (aspartate kinase, aspartate-semialdehyde dehydrogenase, homoserine dehydrogenase) feeds both threonine and methionine. Yeast HOM3/HOM2/HOM6 are monofunctional whereas E. coli ThrA/MetL and plant AK-HSDH are bifunctional fusions; THR1/THR4 complete threonine. Lysine is NOT a branch in fungi (unlike bacteria), which is a key generalisation caveat. Aspartate supply (PYC + AAT) belongs to aspartate_asparagine_metabolism. - module: methionine_biosynthesis action: ALIGN scope: L-methionine from homoserine (bacteria, fungi, plants) pathways: [PWY3O-954, PWY-5344, PWY3O-238] gocam: [YeastPathways_PWY3O-954, YeastPathways_PWY-5344, YeastPathways_PWY3O-238, 66a3e0bb00001342] rationale: >- Existing module already has activation/sulfur-incorporation/methylation variants. Fungi: MET2 homoserine O-acetyltransferase, MET17 direct sulfhydrylase, MET6 cobalamin-independent methionine synthase using MET13/MET12 + MET7 polyglutamate folate. - module: fungal_sulfur_amino_acid_transsulfuration action: NEW scope: bidirectional transsulfuration in fungi (forward CBS/CGL and reverse CGS/CBL) pathways: [PWY-821-1, HOMOCYS-CYS-CONVERT, CYSTEINE-SYN2-PWY, HOMOCYSDEGR-PWY-1] gocam: [YeastPathways_PWY-821-1, YeastPathways_HOMOCYS-CYS-CONVERT, YeastPathways_CYSTEINE-SYN2-PWY, YeastPathways_HOMOCYSDEGR-PWY-1] rationale: >- homocysteine_metabolism is human-specific (remethylation + forward transsulfuration). S. cerevisiae makes cysteine only by forward transsulfuration (CYS4, CYS3) but also runs the reverse direction (STR2, STR3), so a bidirectional module is the right generalisation for fungi; the forward arm conforms to the animal CBS/CGL arm. Named for its scope; linked to homocysteine_metabolism via notes. - module: aps_dependent_assimilatory_sulfate_reduction action: ALIGN scope: assimilatory sulfate reduction (APS and PAPS branches) pathways: [SO4ASSIM-PWY, PWY-781, PWY-5340] gocam: [YeastPathways_SO4ASSIM-PWY, YeastPathways_PWY-781, YeastPathways_PWY-5340, 66a3e0bb00001342] rationale: >- The existing module explicitly models only the APS-reductase branch and calls PAPS the alternative. Fungi use the PAPS branch (MET14 APS kinase, MET16 PAPS reductase) and a NADPH sulfite reductase MET10/MET5. Add the PAPS branch as a variant rather than creating a second module; PAPS activation for sulfonation (PWY-5340) is the MET3+MET14 prefix. - module: siroheme_biosynthesis action: NEW scope: uroporphyrinogen III -> siroheme (bacteria CysG, fungi Met1+Met8, plants) pathways: [PWY-5194-1] gocam: [YeastPathways_PWY-5194-1] rationale: >- Three reactions (SAM-dependent bis-methylation, dehydrogenation, ferrochelation) with fused (CysG) and split (MET1 + MET8) architectures; cofactor supply for sulfite reductase. Shares uroporphyrinogen III with heme. - module: methionine_cycle action: ALIGN scope: taxon-neutral SAM cycle pathways: [PWY-5041, SAM-PWY] gocam: [YeastPathways_PWY-5041, 69c59f8a00000584] rationale: >- Existing module is taxon-neutral; add SAM1/SAM2, SAH1, MET6 and fission yeast exemplars. SAM biosynthesis (single MAT reaction) folds in. - module: methionine_salvage_mta_cycle action: NEW scope: universal 5'-methylthioadenosine (MTA) cycle pathways: [PWY3O-64, PWY3O-351] gocam: [YeastPathways_PWY3O-64, YeastPathways_PWY3O-351] rationale: >- Six-step MTA cycle (MEU1 MTA phosphorylase, MRI1 isomerase, MDE1 dehydratase, UTR4 enolase-phosphatase, ADI1 dioxygenase, ARO8/BAT transamination). YeastCyc attaches only the transaminases; the remaining enzymes are well characterised in yeast and must be added. The superpathway frame adds polyamine synthesis, which is a separate module. - module: proline_metabolism action: GENERALIZE scope: eukaryotic proline-P5C cycle (fungi, animals, plants) pathways: [PROSYN-PWY, PROUT-PWY] gocam: [YeastPathways_PROSYN-PWY, YeastPathways_PROUT-PWY, 678073a900003902] rationale: >- The chemistry is identical; only the architecture differs (yeast PRO1 gamma-glutamyl kinase + PRO2 gamma-glutamyl-phosphate reductase vs. the fused animal/plant P5CS; PUT1/PUT2 vs. PRODH/ALDH4A1). Broaden the existing module with a split-P5CS variant. - module: arginine_catabolism_arginase_pathway action: NEW scope: arginase -> ornithine aminotransferase -> P5C -> glutamate (fungi, plants, animals) pathways: [ARGDEG-YEAST-PWY, ARG-PRO-PWY] gocam: [YeastPathways_ARGDEG-YEAST-PWY, YeastPathways_ARG-PRO-PWY] rationale: >- Arginine as a nitrogen source: CAR1 arginase, CAR2 ornithine aminotransferase, spontaneous cyclisation, then PUT2 (or PRO3 back to proline). Shares P5C with proline_metabolism; the urea product feeds ureide/urea catabolism. - module: nitrogen_assimilation_glutamate_glutamine action: NEW scope: eukaryotic microbial ammonium assimilation (GDH + GS/GOGAT) and glutamate catabolism pathways: [PWY3O-13, GLUNH3-PWY, GLNSYN-PWY, GLUGLNSYN-PWY, PWY-3322] gocam: [YeastPathways_PWY3O-13, 67c10cc400000148] rationale: >- bacterial_ammonia_assimilation is bacterial GS-GOGAT only and glutamate_glutamine_ammonia_hub is human (no GOGAT, mitochondrial GDH). Fungi assimilate ammonium chiefly by NADP-GDH (GDH1/GDH3) plus GS (GLN1) and NADH-GOGAT (GLT1), with NAD-GDH (GDH2) for catabolism and 2-oxoglutarate from IDH/IDP. A fungal-scope module with assimilation variants (GDH vs GS-GOGAT) is the honest level; conformance notes link the bacterial GS-GOGAT module. - module: aspartate_asparagine_metabolism action: NEW scope: aspartate and asparagine synthesis and turnover (eukaryotes) pathways: [ASPBIO-PWY, ASPARTATESYN-PWY, ASPARAGINE-BIOSYNTHESIS-1, ASPARAGINE-DEG2-PWY, ALANINE-SYN2-PWY, ALANINE-DEG3-PWY] gocam: [YeastPathways_ASPBIO-PWY, YeastPathways_ASPARAGINE-BIOSYNTHESIS-1, YeastPathways_ASPARAGINE-DEG2-PWY, 67c10cc400005826] rationale: >- Single-reaction YeastCyc frames (AAT transamination, ASN1/ASN2 asparagine synthetase, ASP1/ASP3 asparaginases, ALT1 alanine transaminase) are folded into one transamination/amidation module rather than five one-enzyme modules. Pyruvate carboxylation (PYC) is upstream and lives in pyruvate_metabolism. - module: ehrlich_pathway action: NEW scope: fungal amino-acid catabolism to fusel alcohols/acids (Ehrlich pathway) pathways: [PWY3O-4109, PWY3O-4112, PWY3O-4105, PWY3O-4115, PWY3O-4108, PWY3O-214] gocam: [YeastPathways_PWY3O-4109, YeastPathways_PWY3O-4112, YeastPathways_PWY3O-4105, YeastPathways_PWY3O-4115, YeastPathways_PWY3O-4108, YeastPathways_PWY3O-214] rationale: >- Six YeastCyc frames (Ile, Leu, Val, Phe, Tyr, Trp degradation) are one three-step pathway with substrate variants: transamination (BAT1/BAT2 for BCAA, ARO8/ARO9 for aromatics) -> thiamine-dependent 2-oxoacid decarboxylation (ARO10, PDC1/5/6) -> reduction (ADH) or oxidation (ALD). YeastCyc omits ARO10, the main phenylpyruvate decarboxylase; it must be added. The superpathway structure is the right generalisation, with substrate as the variant axis. - module: gaba_shunt action: GENERALIZE scope: GABA shunt in fungi, plants and animals pathways: [GLUDEG-I-PWY-1, YEAST-4AMINOBUTMETAB-PWY] gocam: [YeastPathways_GLUDEG-I-PWY-1, YeastPathways_YEAST-4AMINOBUTMETAB-PWY, 696022cd00001857] rationale: >- Same three activities (GAD1, UGA1, UGA2) in yeast; module is labelled mammalian. Broaden with fungal exemplars while keeping the neuronal context as a lineage note. - module: polyamine_metabolism action: GENERALIZE scope: eukaryotic polyamine biosynthesis pathways: [POLYAMSYN-YEAST-PWY, BSUBPOLYAMSYN-PWY, ARGSPECAT-PWY, PWY-46] gocam: [YeastPathways_POLYAMSYN-YEAST-PWY, YeastPathways_BSUBPOLYAMSYN-PWY, YeastPathways_ARGSPECAT-PWY, 67b1629100004168] rationale: >- SPE1 ODC, SPE2 AdoMetDC, SPE3/SPE4 aminopropyltransferases, FMS1 polyamine oxidase (back-conversion, also beta-alanine source) are orthologous to the human set; add fungal exemplars. - module: ureide_urea_catabolism action: NEW scope: purine ring nitrogen recovery (allantoin -> urea -> NH3/CO2) with urease vs urea amidolyase variants pathways: [ALLANTOINDEG-PWY, PWY-5694, PWY-5697, PWY-5703] gocam: [YeastPathways_ALLANTOINDEG-PWY, YeastPathways_PWY-5694, YeastPathways_PWY-5697, YeastPathways_PWY-5703, 665912ed00002626] rationale: >- S. cerevisiae lacks urate oxidase and urease: it takes up allantoin and uses DAL1-DAL2-DAL3 then the biotin-dependent urea amidolyase DUR1,2. S. pombe instead has urate oxidase and urease (PomBase model). The right generalisation is one ureide pathway with an entry variant (urate oxidase route present/absent) and a urea-cleavage variant (urease vs. urea carboxylase + allophanate hydrolase). - module: chorismate_superpathway action: NOTE pathways: [ALL-CHORISMATE-PWY-1] rationale: >- Union frame (shikimate + Phe/Tyr + Trp + folate pABA + one-carbon); every reaction is assigned to a component module. Not modelled itself. - module: lysine_catabolism action: NOTE pathways: [LYSDEGII-PWY, PWY-5177] rationale: >- LYSDEGII-PWY has no yeast enzymes in YeastCyc and PWY-5177 has only ERG10 for the final thiolase. S. cerevisiae does not use lysine as a carbon or nitrogen source; these frames are pathway holes/predictions. No module. - module: threonine_serine_deamination action: NOTE pathways: [THREOCAT2-PWY, SERDEG-PWY] rationale: >- CHA1 catabolic serine/threonine dehydratase only (one enzyme); recorded in the ehrlich_pathway/BCAA notes as the catabolic counterpart of ILV1. # ------------------------------------------------------------- central carbon - module: emp_glycolysis action: ALIGN scope: generic EMP glycolysis pathways: [GLYCOLYSIS, PWY3O-3827, PWY3O-0, PWY3O-1743] gocam: [YeastPathways_GLYCOLYSIS, YeastPathways_PWY3O-0, YeastPathways_PWY3O-1743, 663d668500002302] rationale: >- Generic module; add HXK1/HXK2/GLK1, PGI1, PFK1/PFK2 hetero-octamer, FBA1, TPI1, TDH1-3, PGK1, GPM1, ENO1/2, CDC19/PYK2 and fission yeast exemplars. Fructose and mannose entry frames (hexokinase, PMI40) fold in as entry points. - module: alcoholic_fermentation action: NEW scope: pyruvate -> acetaldehyde -> ethanol (yeasts, plants under hypoxia, Zymomonas) pathways: [GLUCFERMEN-PWY, PWY3O-440, PWY3O-335, PWY3O-981, PWY3O-661, PWY3O-246] gocam: [YeastPathways_GLUCFERMEN-PWY, YeastPathways_PWY3O-440, YeastPathways_PWY3O-335, YeastPathways_PWY3O-981, 678073a900000393] rationale: >- Two-step NAD+-regenerating branch (PDC1/5/6 + ADH1) downstream of glycolysis, with the acetoin/2,3-butanediol carboligation side branch (PDC side activity, BDH1) folded in as an optional branch. The superpathway frame is glycolysis + this module. - module: pdh_bypass_acetyl_coa_synthesis action: NEW scope: cytosolic acetyl-CoA via pyruvate decarboxylase/acetaldehyde dehydrogenase/acetyl-CoA synthetase; ethanol reutilisation pathways: [PWY3O-4300, ACETATEUTIL2-PWY] gocam: [YeastPathways_PWY3O-4300] rationale: >- Fungi lack ATP-citrate lyase (in S. cerevisiae) and make cytosolic acetyl-CoA by PDC -> ALD6 -> ACS1/ACS2; on ethanol, ADH2 feeds the same chain. Distinct from alcoholic fermentation (opposite direction) and from mitochondrial PDH. - module: gluconeogenesis action: ALIGN scope: generic gluconeogenesis pathways: [GLUCONEO-PWY-1] gocam: [YeastPathways_GLUCONEO-PWY-1] rationale: Add PYC1/2, PCK1, FBP1, MDH2 and the glycolytic reversible enzymes. - module: tca_cycle action: ALIGN scope: generic TCA cycle pathways: [TCA-EUK-PWY, PWY-5084, PWY3O-94] gocam: [YeastPathways_TCA-EUK-PWY, YeastPathways_PWY-5084, YeastPathways_PWY3O-94, 665912ed00000015] rationale: >- Add yeast/fission yeast exemplars (CIT1, ACO1, IDH1/IDH2 NAD-IDH, KGD1/KGD2/ LPD1, LSC1/LSC2, SDH1-4, FUM1, MDH1). The superpathway frame adds the glyoxylate cycle, a separate module. - module: glyoxylate_cycle action: NEW scope: isocitrate lyase + malate synthase bypass (bacteria, fungi, plants, nematodes) pathways: [GLYOXYLATE-BYPASS] gocam: [YeastPathways_GLYOXYLATE-BYPASS] rationale: >- Two signature enzymes (ICL1, MLS1/DAL7) plus shared citrate synthase (peroxisomal CIT2), aconitase and malate dehydrogenase (MDH3), with the fungal compartmental split (peroxisome/cytosol) as context. glycolate_glyoxylate_assimilation is a different bacterial pathway. - module: pyruvate_metabolism action: ALIGN scope: mitochondrial pyruvate fates (PDH + PC) pathways: [PYRUVDEHYD-PWY] gocam: [YeastPathways_PYRUVDEHYD-PWY, 67086be200000251] rationale: Add PDA1/PDB1/LAT1/LPD1/PDX1 and PYC1/PYC2 (cytosolic in yeast). - module: pentose_phosphate_pathway action: ALIGN scope: generic PPP (oxidative + non-oxidative + PRPP) pathways: [PENTOSE-P-PWY, OXIDATIVEPENT-PWY, NONOXIPENT-PWY, PWY0-662] gocam: [YeastPathways_PENTOSE-P-PWY, YeastPathways_OXIDATIVEPENT-PWY, YeastPathways_NONOXIPENT-PWY, 67b1629100000953] rationale: >- Add ZWF1, SOL3/SOL4, GND1/GND2, RPE1, RKI1, TKL1/2, TAL1/NQM1 and PRS1-5. YeastCyc omits the lactonases and 6PGDH in its gene lists; they must be added from literature. - module: glycerol_metabolism action: NEW scope: glycerol synthesis (G3P dehydrogenase + G3P phosphatase) and utilisation (glycerol kinase + G3P oxidase/dehydrogenase) in eukaryotic microbes pathways: [PWY3O-48, AERO-GLYCEROL-CAT-PWY] gocam: [YeastPathways_AERO-GLYCEROL-CAT-PWY, 6796b94c00004743] rationale: >- Synthesis (GPD1/GPD2 + GPP1/GPP2; osmoprotection and redox balance) and utilisation (GUT1 + mitochondrial FAD-GUT2) share glycerol-3-phosphate; glycerol_phosphate_shuttle (human) is the redox-shuttle subset. - module: galactose_leloir_pathway action: ALIGN scope: generic Leloir pathway pathways: [YEAST-GALACT-METAB-PWY] gocam: [YeastPathways_YEAST-GALACT-METAB-PWY, 6796b94c00002484] rationale: Add GAL1, GAL7, GAL10 (fused epimerase/mutarotase), PGM1/PGM2. - module: xylose_oxidoreductase_pathway action: NEW scope: D-xylose -> xylitol -> D-xylulose -> D-xylulose 5-P (fungal oxidoreductase route) vs. bacterial xylose isomerase pathways: [PWY3O-8, PWY3O-5] gocam: [YeastPathways_PWY3O-8] rationale: >- GRE3 aldose reductase, XYL2 xylitol dehydrogenase, XKS1 xylulokinase; the isomerase route is the alternative entry. S. cerevisiae runs the pathway poorly, which belongs in notes. - module: trehalose_metabolism action: NEW scope: TPS/TPP (OtsA/OtsB) trehalose synthesis and trehalase hydrolysis (fungi, bacteria, plants, insects) pathways: [TRESYN-PWY, TREDEG-YEAST-PWY] gocam: [YeastPathways_TRESYN-PWY, 6882d2b800002884] rationale: >- TPS1/TPS2 within the TPS complex with TSL1/TPS3 regulatory subunits; neutral (NTH1) and acid (ATH1) trehalases. Alternative trehalose routes (TreY/TreZ, TreS) are other modules. - module: glycogen_metabolism_fungal action: NEW scope: fungal glycogen synthesis and mobilisation pathways: [PWY3O-4031, GLYCOCAT-YEAST-PWY] gocam: [YeastPathways_PWY3O-4031, YeastPathways_GLYCOCAT-YEAST-PWY] rationale: >- The human modules are disease-oriented and split; the bacterial one uses ADP-glucose. Fungi use UDP-glucose (UGP1), glycogenin priming (GLG1/GLG2, omitted by YeastCyc), GSY1/GSY2, GLC3 branching, GPH1 phosphorylase, GDB1 debranching and vacuolar SGA1. Conform to the human glycogen modules in notes rather than editing them. - module: udp_glucose_and_udp_galactose_biosynthesis action: FOLD pathways: [] rationale: UGP1/PGM steps appear in the glycogen and Leloir frames; no separate YeastCyc frame. - module: hexosamine_biosynthesis action: ALIGN scope: eukaryotic hexosamine pathway pathways: [UDPNAGSYN-YEAST-PWY] gocam: [YeastPathways_UDPNAGSYN-YEAST-PWY, 68b0f0d000008252] rationale: Add GFA1, GNA1, PCM1, QRI1 exemplars. - module: fungal_chitin_chitosan_synthesis action: NEW scope: chitin synthesis and deacetylation in fungi pathways: [PWY3O-15, PWY3O-70] gocam: [YeastPathways_PWY3O-15] rationale: >- Chitin synthase classes (CHS1 repair, CHS2 primary septum, CHS3 lateral wall/chitin ring) and spore-wall chitin deacetylases CDA1/CDA2. Two substantive steps. - module: dolichol_phosphate_sugar_donor_supply action: ALIGN scope: GDP-mannose, Dol-P-Man and Dol-P-Glc supply pathways: [PWY3O-123, PWY3O-1565] gocam: [YeastPathways_PWY3O-123, YeastPathways_PWY3O-1565, 671ae02600003548, 671ae02600003596] rationale: Add PMI40, SEC53, PSA1, DPM1, ALG5, UGP1 and fission yeast exemplars. - module: n_glycan_llo_assembly_cytoplasmic action: ALIGN scope: LLO assembly (cytoplasmic and lumenal modules together) pathways: [GLUCOSE-MANNOSYL-CHITO-DOLICHOL] gocam: [YeastPathways_GLUCOSE-MANNOSYL-CHITO-DOLICHOL, 665912ed00000459] rationale: >- The frame spans both existing LLO modules (cytoplasmic ALG7/ALG13-14/ ALG1/ALG2/ALG11; lumenal ALG3/ALG9/ALG12/ALG6/ALG8/ALG10/DIE2). Align both with yeast exemplars; the ALG names are yeast-derived so this is mostly grounding. - module: n_glycan_llo_assembly_lumenal action: ALIGN scope: lumenal ER LLO extension and glucosylation to Glc3Man9GlcNAc2-PP-Dol pathways: [GLUCOSE-MANNOSYL-CHITO-DOLICHOL] gocam: [YeastPathways_GLUCOSE-MANNOSYL-CHITO-DOLICHOL, 665912ed00000459] rationale: >- Same YeastCyc frame as n_glycan_llo_assembly_cytoplasmic: the source frame spans both faces of the ER and the lumenal ALG3/ALG9/ALG12/ALG6/ALG8/ALG10 steps belong in this existing sister module. - module: methylglyoxal_detoxification action: ALIGN pathways: [PWY-901] gocam: [YeastPathways_PWY-901, 6918f23700001200] rationale: GLO1/GLO2/GLO4 glyoxalase system. - module: glutathione_dependent_formaldehyde_detoxification action: ALIGN pathways: [PWY-1801-1] gocam: [YeastPathways_PWY-1801-1] rationale: SFA1 (GSH-dependent FDH), YJL068C S-formylglutathione hydrolase, FDH1. - module: glutathione_synthesis_gamma_glutamyl_cycle action: ALIGN scope: GSH synthesis and gamma-glutamyl turnover pathways: [GLUTATHIONESYN-PWY, PWYQT-4432, PWY3O-114] gocam: [YeastPathways_GLUTATHIONESYN-PWY, YeastPathways_PWYQT-4432, YeastPathways_PWY3O-114, 68b0f0d000008341] rationale: >- GSH1/GSH2 synthesis (also align glutathione_biosynthesis) and the truncated yeast gamma-glutamyl cycle (ECM38 vacuolar GGT; DUG1/DUG2/DUG3 cytosolic degradation, absent from YeastCyc). - module: glutathione_biosynthesis action: ALIGN scope: two-step GSH biosynthesis pathways: [GLUTATHIONESYN-PWY] gocam: [YeastPathways_GLUTATHIONESYN-PWY, 68b0f0d000008341] rationale: >- Same GSH1/GSH2 source frame as glutathione_synthesis_gamma_glutamyl_cycle; keep the legacy biosynthesis-only module aligned for consumers that need only the canonical two-step GSH synthesis branch. - module: glutathione_thioredoxin_redox_systems action: NEW scope: NADPH-dependent glutathione/glutaredoxin and thioredoxin systems with peroxide scavenging pathways: [GLUT-REDOX2-PWY, PWY3O-592, THIOREDOX-PWY, DETOX1-PWY] gocam: [YeastPathways_GLUT-REDOX2-PWY, YeastPathways_PWY3O-592, YeastPathways_THIOREDOX-PWY, YeastPathways_DETOX1-PWY] rationale: >- Two parallel NADPH-driven thiol reduction systems (GLR1 -> GSH -> glutaredoxins/GPX-like; TRR1/TRR2 -> TRX1/TRX2/TRX3 -> peroxiredoxins/ HYR1 (GPX3, a thiol peroxidase not a GSH peroxidase) and catalase as the thiol-independent peroxide sink. YeastCyc's "superoxide radicals degradation" lists only catalases; superoxide dismutases must be checked. # ----------------------------------------------------------------- cofactors - module: tetrahydrofolate_biosynthesis action: NEW scope: de novo THF and polyglutamate synthesis in microbes and plants pathways: [FOLSYN-PWY-1, PWY-6147, PWY3O-45, PWY-6614, PWY-6543, PWY3O-1874, PWY3O-20] gocam: [YeastPathways_FOLSYN-PWY-1, YeastPathways_PWY-6147, YeastPathways_PWY3O-45, YeastPathways_PWY-6614, YeastPathways_PWY-6543, YeastPathways_PWY3O-1874, YeastPathways_PWY3O-20, 66a3e0bb00002988, "6870555700003085"] rationale: >- Pterin branch (FOL2 GTP cyclohydrolase I, FOL1 trifunctional DHNA/HPPK/ DHPS fusion), pABA branch (ABZ1/ABZ2), FOL3 DHFS, DFR1 DHFR and MET7 FPGS. Fungal FOL1 fusion vs bacterial FolB/FolK/FolP is the main variant. - module: folate_one_carbon_interconversion action: ALIGN pathways: [PWY3O-697, PWY-2201] gocam: [YeastPathways_PWY3O-697, YeastPathways_PWY-2201] rationale: >- Add ADE3/MIS1 trifunctional C1-THF synthases, MTD1 NAD-dependent dehydrogenase, MET12/MET13, FAU1, SHM1/SHM2 exemplars. - module: glycine_cleavage_system action: ALIGN pathways: [GLYCLEAV-PWY] gocam: [YeastPathways_GLYCLEAV-PWY, 67b1629100001554] rationale: GCV1/GCV2/GCV3/LPD1. - module: riboflavin_biosynthesis action: ALIGN scope: de novo riboflavin and FMN/FAD pathways: [YEAST-RIBOSYN-PWY] gocam: [YeastPathways_YEAST-RIBOSYN-PWY, 6796b94c00000731] rationale: >- Fungal order of pyrimidine-branch reactions differs (RIB7 reduction before RIB2 deamination); FMN1 riboflavin kinase and FAD1 FAD synthetase are monofunctional, unlike bacterial RibF. Add as variants. - module: eukaryotic_thiamine_biosynthesis action: NEW scope: THI4/THI5-type thiamine synthesis in fungi (and plants for THI4) pathways: [PWY3O-17] gocam: [YeastPathways_PWY3O-17, 66c7d41500000963] rationale: >- Fundamentally different from the bacterial module: THI4 is a single turnover suicide thiazole synthase using its own Cys205 sulfur, THI5 family makes HMP-P from histidine and PLP, THI6 fuses thiazole kinase and thiamine-phosphate synthase, THI20/21 HMP-P kinases, THI80 thiamine pyrophosphokinase. YeastCyc lists only THI6 and THI80 gene products. - module: vitamin_b6_plp_metabolism action: GENERALIZE scope: B6 salvage (eukaryotes) plus pointer to the PdxS/PdxT de novo route pathways: [PLPSAL-PWY] gocam: [YeastPathways_PLPSAL-PWY, 66c7d41500001171] rationale: >- PDX3 PNP/PMP oxidase and BUD16 pyridoxal kinase. Yeasts also synthesise PLP de novo via SNZ1/SNO1 (PdxS/PdxT), missing from YeastCyc; record as the de novo entry variant. - module: biotin_biosynthesis action: ALIGN scope: biotin ring assembly (BioF/BioA/BioD/BioB) with lineage-specific pimelate supply pathways: [BIOTIN-SYNTHESIS-PWY] gocam: [YeastPathways_BIOTIN-SYNTHESIS-PWY, 67c10cc400002026] rationale: >- Fungal BIO6 (KAPA synthase), BIO3 (DAPA aminotransferase), BIO4 (DTB synthetase), BIO2 (biotin synthase); pimeloyl-CoA source (BIO1) differs from the BioC-BioH route and S. cerevisiae lab strains are often auxotrophic. Add a fungal pimeloyl-CoA variant. - module: coenzyme_a_biosynthesis action: ALIGN scope: pantoate-derived CoA with a polyamine-derived beta-alanine variant pathways: [PANTOSYN2-PWY, PWY-5760-1] gocam: [YeastPathways_PANTOSYN2-PWY, YeastPathways_PWY-5760-1, 678073a900002636, 67b1629100001098] rationale: >- Yeast beta-alanine comes from spermine via FMS1 polyamine oxidase and ALD2/ALD3, not aspartate decarboxylation (PanD) -- a beta-alanine supply variant. ECM31, PAN6, CAB1-CAB5 complete CoA. - module: nad_de_novo_and_salvage_fungal action: NEW scope: kynurenine de novo NAD+ plus nicotinamide/NR salvage in fungi pathways: [PWY3O-4158, NADSYN-PWY, TRYPTOPHAN-DEGRADATION-1, PWY-5651, PWY-5653, PWY3O-4106, PWY3O-4107, PWY3O-96, PWY3O-224, PWY3O-236] gocam: [YeastPathways_PWY3O-4158, YeastPathways_NADSYN-PWY, YeastPathways_TRYPTOPHAN-DEGRADATION-1, YeastPathways_PWY-5651, YeastPathways_PWY-5653, YeastPathways_PWY3O-4106, YeastPathways_PWY3O-4107, 698e557b00000821] rationale: >- Ten YeastCyc frames are one NAD+ supply network converging on NaMN/NMN: de novo BNA1-BNA7 kynurenine route (also kynurenine_nad_de_novo, human), the PNC1-NPT1 Preiss-Handler salvage, NRK1/URH1/PNP1 riboside salvage, and NMA1/NMA2 + QNS1 to NAD+. Existing nad_biosynthesis_salvage is the aspartate de novo route and does not apply (fungi lack NadA/NadB). Model routes as variants converging on shared NMNAT and NAD synthetase steps. - module: heme_biosynthesis action: ALIGN scope: cross-taxon heme B biosynthesis pathways: [HEME-BIOSYNTHESIS-II, PWY3O-50, PWY3O-69] gocam: [YeastPathways_HEME-BIOSYNTHESIS-II, YeastPathways_PWY3O-50, YeastPathways_PWY3O-69, 66c7d41500000841] rationale: Add HEM1 (Shemin ALA synthase) through HEM15; siroheme is its own module. - module: ubiquinone_biosynthesis action: GENERALIZE scope: CoQ biosynthesis in bacteria and eukaryotes pathways: [PWY3O-862, PWY3O-19, PWY3O-1109, HEXPPSYN-PWY-2] gocam: [YeastPathways_PWY3O-862, YeastPathways_PWY3O-19, YeastPathways_PWY3O-1109, YeastPathways_HEXPPSYN-PWY-2, 662af8fa00000408] rationale: >- The bacterial module and the human coenzyme_q10 module describe the same ring chemistry; the eukaryotic CoQ synthome (COQ3-COQ9, COQ11) differs in decarboxylation/hydroxylation enzymes (COQ6, COQ7, unknown decarboxylase) and 4-HB supply (from tyrosine via ARO8/ARO9, ARO10, HFD1 in yeast; the PWY3O-1109 frame has no assigned genes). Add a eukaryotic variant to the bacterial-scoped module only if it stays coherent; otherwise create a eukaryotic sibling. - module: isoprenoid_diphosphate_biosynthesis action: ALIGN pathways: [PWY-5123] gocam: [YeastPathways_PWY-5123, 662af8fa00000499] rationale: IDI1, ERG20 (GPP/FPP), BTS1 (GGPP), COQ1 (hexaprenyl-PP). - module: mevalonate_pathway action: GENERALIZE pathways: [IPPSYN-PWY, PWY-922] gocam: [YeastPathways_IPPSYN-PWY, YeastPathways_PWY-922, 662af8fa00000499] rationale: ERG10, ERG13, HMG1/HMG2, ERG12, ERG8, MVD1 (ERG19), IDI1; module already mentions yeast. - module: ergosterol_biosynthesis action: NEW scope: fungal sterol synthesis from squalene to ergosterol, with conformance to the cholesterol post-lanosterol core pathways: [ERGOSTEROL-SYN-PWY-1, PWY3O-31704, PWY-6075-1, PWY-6074-1, PWY-5670-1, PWY-6132] gocam: [YeastPathways_ERGOSTEROL-SYN-PWY-1, YeastPathways_PWY3O-31704, YeastPathways_PWY-6075-1, YeastPathways_PWY-6074-1, YeastPathways_PWY-5670-1, 66c7d41500002088] rationale: >- Six YeastCyc frames are one pathway. Generalisation: the squalene -> lanosterol -> zymosterol core (ERG9, ERG1, ERG7, ERG11/CYP51, ERG24, C4-demethylation complex ERG25/ERG26/ERG27 scaffolded by ERG28) is shared with animals; the ergosterol-specific tail (ERG6 C24-methylation, ERG2, ERG3, ERG5, ERG4) defines the fungal branch. Model the shared core as parts conforming to the human sterol modules. - module: fatty_acid_de_novo_synthesis action: GENERALIZE scope: eukaryotic cytosolic de novo fatty acid synthesis (type I FAS) pathways: [PWY3O-5962, PWY3O-6336, PWY3O-10, PWY-5971-1, PWY3O-8514, PWY3O-355, PWY3O-31723, PWY3O-5268, PWY3O-1801] gocam: [YeastPathways_PWY3O-5962, YeastPathways_PWY3O-6336, YeastPathways_PWY3O-10, YeastPathways_PWY-5971-1, YeastPathways_PWY3O-8514, YeastPathways_PWY3O-355, YeastPathways_PWY3O-5268, YeastPathways_PWY3O-1801, 678073a900002931] rationale: >- Nine YeastCyc frames (initial steps, myristate, palmitate, stearate, oleate, palmitoleate, superpathways) are one pathway. Add the fungal alpha6beta6 FAS (FAS1/FAS2) as a variant of the animal FASN megasynthase, ACC1 carboxylase, and OLE1 delta-9 desaturation as an optional final part. The mitochondrial FAS II part (CEM1, OAR1, MCT1, HFA1) is assigned to type_ii_fatty_acid_synthesis. - module: type_ii_fatty_acid_synthesis action: ALIGN scope: dissociated FAS II including mitochondrial FAS II (octanoyl-ACP for lipoate) pathways: [FASYN-ELONG2-PWY] gocam: [YeastPathways_FASYN-ELONG2-PWY] rationale: >- YeastCyc's "fatty acid elongation" frame is actually the mitochondrial FAS II (CEM1, OAR1, HTD2, ETR1, MCT1, ACP1) mixed with FAS1/FAS2 steps. Add a mitochondrial FAS II variant. - module: fatty_acid_elongation_cycle action: ALIGN pathways: [PWY-5080-1] gocam: [YeastPathways_PWY-5080-1] rationale: ELO1/ELO2/ELO3, IFA38, PHS1, TSC13 (YeastCyc lists ELO2 only). - module: peroxisomal_beta_oxidation action: ALIGN pathways: [YEAST-FAO-PWY] gocam: [YeastPathways_YEAST-FAO-PWY] rationale: >- In fungi like S. cerevisiae beta-oxidation is exclusively peroxisomal (POX1, FOX2, POT1, ECI1, DCI1; FAA/FAT activation). Add as the peroxisome-only variant. - module: carnitine_shuttle action: GENERALIZE scope: carnitine acyltransferase shuttles (mitochondrial LCFA import in animals; acetyl-carnitine shuttle in fungi) pathways: [PWY3O-4] gocam: [YeastPathways_PWY3O-4] rationale: >- Yeast CAT2/YAT1/YAT2 + CRC1 move acetyl units from peroxisome/cytosol into mitochondria; same chemistry, different cargo. Add as a variant. - module: triacylglycerol_biosynthesis action: GENERALIZE scope: glycerolipid/TAG synthesis (G3P and DHAP routes) pathways: [TRIGLSYN-PWY, PWY3O-6635, PWY3O-6407, PWY3O-6499] gocam: [YeastPathways_TRIGLSYN-PWY, YeastPathways_PWY3O-6635, YeastPathways_PWY3O-6407, YeastPathways_PWY3O-6499, 6796b94c00005663] rationale: >- GPT2/SCT1 (G3P/DHAP acyltransferases), AYR1 (acyl-DHAP reductase), SLC1/ALE1, PAH1 lipin, DGA1 + LRO1 (PDAT, acyl-CoA-independent). Add DHAP-route and PDAT variants. - module: cdp_dag_phospholipid_synthesis action: NEW scope: CDP-diacylglycerol-dependent phospholipid synthesis (PS, PE, PC via methylation, PI, PG, CL) in fungi and bacteria pathways: [PHOSLIPSYN2-PWY-1, PWY3O-2, PHOS-PWY, PWY-5669, PWY3O-103, PWY3O-3] gocam: [YeastPathways_PHOSLIPSYN2-PWY-1, YeastPathways_PWY3O-2, YeastPathways_PHOS-PWY, YeastPathways_PWY-5669, 6796b94c00000009, 67086be200000363] rationale: >- CDS1 -> CHO1 (PS synthase) -> PSD1/PSD2 -> CHO2/OPI3 PE methylation, plus PIS1 and PGS1 -> GEP4 -> CRD1. The bacterial PE and PG/CL modules are the prokaryotic equivalents; the Kennedy pathway is the parallel route. The PC/PE Kennedy frames are assigned to kennedy_pathway_phospholipid_synthesis. - module: kennedy_pathway_phospholipid_synthesis action: GENERALIZE pathways: [PWY3O-450, PWY3O-259] gocam: [YeastPathways_PWY3O-450, YeastPathways_PWY3O-259] rationale: CKI1/EKI1, PCT1/ECT1, CPT1/EPT1 orthologs of the human branches. - module: phosphoinositide_biosynthesis action: NEW scope: PI -> PI3P/PI4P -> PI(3,5)P2/PI(4,5)P2 kinase network in eukaryotes pathways: [PWY3O-242] gocam: [YeastPathways_PWY3O-242, 663d668500002178] rationale: >- Compartment-specific kinase set (VPS34 endosomal PI3K, PIK1 Golgi and STT4 plasma membrane PI4K, MSS4 PI4P5K, FAB1 PI3P5K) with phosphatases outside the boundary. - module: myo_inositol_and_inositol_phosphate_biosynthesis action: NEW scope: de novo myo-inositol (MIPS + IMPase) and the PLC/IPMK/IPK1 inositol phosphate route pathways: [PWY-2301, PWY3O-402] gocam: [YeastPathways_PWY-2301, YeastPathways_PWY3O-402] rationale: >- INO1 + INM1 make myo-inositol; PLC1 -> ARG82 (IPMK) -> IPK1 -> KCS1/VIP1 inositol pyrophosphates. YeastCyc gene list lacks ARG82/KCS1/VIP1. - module: phospholipid_degradation action: NOTE pathways: [LIPASYN-PWY-1] rationale: >- Grab-bag of unrelated phospholipases (PLC1, SPO14, ISC1) with no shared pathway logic; each is covered in phosphoinositide or sphingolipid modules. - module: sphingolipid_de_novo_synthesis action: GENERALIZE scope: ceramide core in eukaryotes, with fungal inositolphosphoceramide head groups pathways: [SPHINGOLIPID-SYN-PWY-1] gocam: [YeastPathways_SPHINGOLIPID-SYN-PWY-1, 67086be200002266] rationale: >- LCB1/LCB2/TSC3 SPT, TSC10, SUR2 C4-hydroxylation (phytosphingosine, fungal/plant), LAG1/LAC1 ceramide synthase, SCS7; then AUR1-KEI1 IPC synthase, CSG1/CSG2, IPT1. LCB kinases/DPL1/YSR3 and YPC1/YDC1 are the degradation/LCB-phosphate branch. Ceramide core conforms to the human module; add a fungal head-group extension. # ------------------------------------------------------------- nucleotides - module: de_novo_purine_synthesis action: ALIGN pathways: [PWY-6122-1, PWY-6123-1, DENOVOPURINE2-PWY, DENOVOPURINE3-PWY, PRPP-PWY-1] gocam: [YeastPathways_PWY-6122-1, YeastPathways_PWY-6123-1, YeastPathways_DENOVOPURINE2-PWY, YeastPathways_DENOVOPURINE3-PWY, YeastPathways_PRPP-PWY-1, 663d668500001911] rationale: >- ADE4 ... ADE16/ADE17; fungal ADE5,7 bifunctional GARS-AIRS and the ADE2 PurK-PurE fusion (class I AIR carboxylase route) are variants. PRPP-PWY-1 superpathway is the union of His, purine and pyrimidine modules. - module: purine_nucleotide_interconversion action: GENERALIZE pathways: [PWY-7219, PWY-7221, PWY-6126-1, PWY-6125] gocam: [YeastPathways_PWY-7219, YeastPathways_PWY-7221, YeastPathways_PWY-6126-1, YeastPathways_PWY-6125] rationale: ADE12, ADE13, IMD2-4, GUA1, ADK1/ADK2, GUK1, YNK1. - module: dntp_de_novo_synthesis action: NEW scope: class Ia ribonucleotide reduction and dNTP formation in eukaryotes pathways: [PWY-7220-1, PWY-7222-1, YEAST-DE-NOVO-PYRMID-DNT] gocam: [YeastPathways_PWY-7220-1, YeastPathways_PWY-7222-1, YeastPathways_YEAST-DE-NOVO-PYRMID-DNT] rationale: >- RNR (RNR1/RNR3 alpha2 + RNR2/RNR4 heterodimeric beta), NDP kinase YNK1, and the dTTP branch (DUT1, CDC21 thymidylate synthase, CDC8 TMP kinase, shared with thymidylate_synthesis). mitochondrial_dntp_supply is the human mito-specific counterpart. - module: de_novo_pyrimidine_synthesis action: ALIGN pathways: [PWY-5686-1, PYRIMID-RNTSYN-PWY, PWY0-162, PWY-7176] gocam: [YeastPathways_PWY-5686-1, YeastPathways_PYRIMID-RNTSYN-PWY, YeastPathways_PWY0-162, YeastPathways_PWY-7176] rationale: >- URA2 (CPSase-ATCase with inactive DHOase domain), URA4 DHOase, URA1 cytosolic fumarate-dependent (class 1A) DHODH (S. pombe Ura3 is the mitochondrial class 2 type), URA5/URA10, URA3. UMP -> UTP -> CTP (URA6, YNK1, URA7/URA8) folded in as a downstream part. - module: purine_salvage_and_catabolism action: GENERALIZE pathways: [PWY3O-1, PWY3O-2220, PWY3O-743, PWY3O-285] gocam: [YeastPathways_PWY3O-1, YeastPathways_PWY3O-2220, YeastPathways_PWY3O-743, YeastPathways_PWY3O-285, 680ad14200001682] rationale: >- APT1, HPT1, XPT1, AAH1 (adenine deaminase, fungal; humans lack it), AMD1, ADO1, PNP1. S. cerevisiae has no xanthine oxidase -- the catabolic arm to urate is absent, so the module needs a salvage-only realisation. - module: pyrimidine_salvage action: NEW scope: pyrimidine base/nucleoside salvage in fungi pathways: [YEAST-RNT-SALV, YEAST-SALV-PYRMID-DNTP] gocam: [YeastPathways_YEAST-RNT-SALV, YeastPathways_YEAST-SALV-PYRMID-DNTP, 69a0c46f00003691] rationale: >- FUR1 UPRTase, FCY1 cytosine deaminase, CDD1, URK1, URH1 nucleosidase. S. cerevisiae lacks thymidine kinase, which is why it cannot salvage thymidine -- a defining realisation caveat. - module: thymidylate_synthesis action: FOLD pathways: [] rationale: Grounded via dntp_de_novo_synthesis (CDC21, CDC8, DUT1). # -------------------------------------------------- respiration and misc - module: oxphos action: ALIGN pathways: [PWY3O-188] gocam: [YeastPathways_PWY3O-188, 663d668500000596] rationale: >- S. cerevisiae lacks complex I and uses NDI1/NDE1/NDE2 type II NADH dehydrogenases -- a defining variant to add (S. pombe also lacks complex I). Complexes II-IV via the mitochondrial_complex_* modules. - module: diphthamide_biosynthesis action: NEW scope: eukaryotic/archaeal diphthamide on eEF2 pathways: [PWY-6482-1] gocam: [YeastPathways_PWY-6482-1] rationale: >- DPH1-DPH2-DPH3(KTI11)-DPH4 radical-SAM ACP transfer, DPH5 methylation, DPH7 (RRT2) demethylation, DPH6 amidation. A protein-modification pathway rather than small-molecule metabolism, but a clean multi-step module. - module: erythroascorbate_biosynthesis action: NEW scope: aldonolactone-oxidoreductase route to the fungal ascorbate analogue pathways: [PWY3O-6-1] gocam: [YeastPathways_PWY3O-6-1] rationale: >- ARA1 D-arabinose dehydrogenase + ALO1 D-arabinono-1,4-lactone oxidase; homologous terminal oxidase to animal GULO and plant GLDH. Two steps. - module: sucrose_hydrolysis action: NOTE pathways: [SUCUTIL-PWY-2] rationale: Single extracellular invertase (SUC2); covered in the SUC2 gene review only. - module: periplasmic_nad_degradation action: NOTE pathways: [PERIPLASMA-NAD-DEGRADATION] rationale: >- Single-reaction frame (NPY1-type pyrophosphatase plus phosphatases); covered as a salvage input in nad_de_novo_and_salvage_fungal notes.